Flowable Hydrogel Polyplex Scaffold for Localized Nucleic Acid Release
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Solution Overview
Problem
Existing nucleic acid delivery methods face challenges such as immune recognition, accumulation in first-pass organs, and rapid clearance, limiting effective delivery to human cells, especially in non-enclosed environments like most organs.
Innovation Solution
A scaffold comprising hydrogel particles with polyplexes containing nucleic acids and complexing agents, designed for localized and controlled release, featuring burst-free or sustained release profiles, and optimized for contact with cells to enhance delivery efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If systemic intravenous delivery is used, then nucleic acids can be delivered to multiple organs, but immune recognition and rapid clearance occur
Solution Approach 1:
The invention segments the delivery system by using local injection into specific tissues or organs rather than systemic intravenous delivery. This allows nucleic acids to be delivered directly to the target location, avoiding circulation through the bloodstream and thus reducing immune recognition and rapid clearance while maintaining effectiveness in the target organ.
Solution Approach 2:
The invention uses hydrogel particles as an intermediary carrier system. These particles are injected locally into tissues or organs and serve as a stable platform for delivering nucleic acids directly to target cells, bypassing the need for systemic circulation and reducing immune-mediated clearance while maintaining delivery effectiveness.
2Reliability
If local delivery injection is used, then immune recognition and clearance are reduced, but delivery to specific locations becomes more complex
Solution Approach 1:
The invention creates a universal delivery platform using hydrogel particles that can be injected into various tissues and organs. The same basic particle formulation and injection methodology can be applied across different target locations, simplifying the delivery process while maintaining the benefits of local delivery and reduced immune recognition.
3Productivity
If high concentration of nucleic acids is used, then transfection efficiency is enhanced, but toxicity and aggregation increase
Solution Approach 1:
The invention segments the nucleic acid cargo into multiple hydrogel particles distributed throughout the injection site. This segmentation allows high total concentration of nucleic acids to be delivered while preventing aggregation and reducing local toxicity, as the particles are dispersed throughout the tissue rather than concentrated in a single location.
Solution Approach 2:
The hydrogel particles serve as an intermediary carrier that protects nucleic acids from aggregation and reduces toxicity. The particles provide a stable matrix that distributes nucleic acids evenly, allowing high concentrations to be delivered without the harmful effects of aggregation or localized toxicity that would occur with naked nucleic acid formulations.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The scaffold enables efficient, controlled release of nucleic acids with minimal initial burst, sustained delivery over extended periods, and effective transfection of cells, improving gene delivery and tissue repair in vivo.
Implementation Method 1
polyplexes, which polyplexes comprise one or more copies of one or more nucleic acids and one or more nucleic acid complexing agents
Implementation Method 2
scaffold comprising hydrogel particles, wherein the particles comprise one or more polyplexes
Implementation Method 3
two or more particles are annealed together, wherein annealed together comprises covalent, electrostatic, hydrophobic, mechanical and transamination annealing
Implementation Method 4
irregularly shaped particles that can be annealed and lyophilized to maintain stability
Data Source
AI summary
The present disclosure provides, in part, nucleic acid loaded flowable hydrogels and compositions, systems and methods related thereto, to effectively deliver nucleic acids to cells that contact the flowable hydrogels.